Fludrocortisone Dose in Sepsis
The recommended dose of fludrocortisone in septic shock is 50 μg once daily, administered enterally (via nasogastric tube) for 7 days, in combination with hydrocortisone 200 mg/day intravenously. 1, 2
Key Dosing Parameters
Standard Regimen
- Fludrocortisone: 50 μg tablet once daily via nasogastric tube for 7 days 1, 2, 3
- Hydrocortisone: 50 mg intravenous bolus every 6 hours (total 200 mg/day) 1, 2, 3
- Duration: 7 days at full dose 1, 3
When to Initiate
- Only in vasopressor-unresponsive septic shock: Patients who remain hypotensive despite adequate fluid resuscitation and moderate-to-high dose vasopressor therapy (>0.1 μg/kg/min norepinephrine equivalent) 1, 4
- Do NOT use in sepsis without shock 1
- Do NOT use if hemodynamic stability is achieved with fluids and vasopressors alone 1
Evidence Supporting Fludrocortisone Addition
The combination of hydrocortisone plus fludrocortisone showed mortality benefit in the landmark 2002 trial, where 28-day mortality was reduced from 63% to 53% in non-responders to corticotropin testing (hazard ratio 0.67,95% CI 0.47-0.95) 3. The more recent APROCCHSS trial (2017) used this same combination regimen and demonstrated particular benefit in community-acquired pneumonia-related septic shock, with 90-day mortality reduced from 51% to 39% (OR 0.60,95% CI 0.43-0.83) 2.
Dose-Response Findings
A 2024 phase II trial compared 50 μg, 100 μg, and 200 μg daily doses of fludrocortisone and found no significant difference in time to shock resolution between doses 5. The 28-day mortality rates were numerically similar across groups: 17% (50 μg), 11% (100 μg), and 11% (200 μg) 5. This supports using the standard 50 μg dose rather than higher doses.
Important Caveats and Pitfalls
Absorption Concerns
- Enteral fludrocortisone achieves detectable plasma concentrations in 97% of critically ill patients, though levels vary widely (median 261 ng/L, IQR 156-334) 5
- Despite variable absorption, the standard 50 μg dose remains effective 5
Guideline Evolution
- 2012-2013 Surviving Sepsis Guidelines recommended hydrocortisone alone at 200 mg/day, with no mention of adding fludrocortisone 1
- 2017 SCCM/ESICM Guidelines suggest low-dose IV hydrocortisone <400 mg/day for at least 3 days, acknowledging the combination approach from APROCCHSS 1
- The mineralocorticoid activity of hydrocortisone alone may be insufficient, which is why fludrocortisone addition was studied 3, 6
Tapering
- Taper hydrocortisone (and discontinue fludrocortisone) when vasopressors are no longer required 1
- Gradual taper is recommended rather than abrupt cessation 4
Testing Not Required
- Do NOT use ACTH stimulation testing to determine who should receive corticosteroids 1, 4
- The test does not reliably identify patients who will benefit from therapy 1
Administration Details
- Route: Fludrocortisone is given enterally (tablet via nasogastric tube); hydrocortisone is given intravenously 1, 2, 3
- Hydrocortisone administration: Continuous infusion is preferred over bolus dosing (grade 2D) 1
- Duration: Full 7-day course at maximum dose 1, 3
Pediatric Considerations
The evidence base for fludrocortisone in pediatric septic shock is limited 1. In children, hydrocortisone dosing ranges from 2 mg/kg/day (stress dose) to 50 mg/kg/day (shock dose) depending on severity and adrenal function 1. Specific fludrocortisone dosing recommendations for pediatric septic shock are not well-established in the guidelines reviewed.